Biomedical subjects

L Fielding

Publications and source records attributed to L Fielding.

9 recordsLinked to original sources

PubMed2005

NMR spectra and dynamics of the sodium salt of per(6-thiobenzoic acid)-gamma-cyclodextrin.

The solution-state NMR spectra of a per-6-substituted gamma-cyclodextrin show some interesting dynamic properties. At high temperature (353 K), the (1)H NMR spectrum shows dynamic averaging of the different conformations. This averaging is no longer observed on cooling of the cyclodextrin solution to 278 K, resulting in NMR spectra with a large (1)H and (13)C chemical shift dispersion. The complete assignment of the eight unique glucosyl residues was achieved using COSY, HSQC and exchange spectroscopy. A ROESY spectrum, with a short mixing time to reduce the effects of exchange, gives correlations that lead to the determination of the connectivity of all eight glucosyl residues. On the NMR time-scale, the cyclodextrin is highly dynamic; the lower temperature minimum energy conformation has one of the aromatic rings self-complexed and a distorted cyclodextrin torus.

Magnetic Resonance Spectroscopy↗

PubMed2002

Modified gamma-cyclodextrins and their rocuronium complexes.

A series of per-6-substituted cyclodextrin derivatives was synthesized as synthetic host molecules for rocuronium, a steroidal muscle relaxant. By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo. The isothermal microcalorimetry data are consistent with the biological data supporting the encapsulation mechanism of action. Binary and biphasic complexes are reported with NMR experiments clearly showing free and bound rocuronium. [structure: see text]

Androstanols↗

PubMed2001

NMR diffusion spectroscopy as a measure of host-guest complex association constants and as a probe of complex size.

The complexes of cyclohexylacetic acid and cholic acid with beta-cyclodextrin were studied by NMR diffusion coefficient measurements. The diffusion coefficient of the 1:1 cyclohexylacetic acid/beta-cyclodextrin complex, K(a) = 1800 +/- 100 M(-1), is slightly slower (3.23 +/- 0.07 x 10(-6) cm(2) s(-1)) than that of beta-cyclodextrin (3.29 +/- 0.07 x 10(-6) cm(2) s(-1)). The diffusion coefficient of the 1:1 cholic acid/beta-cyclodextrin complex, K(a) = 5900 +/- 800 M(-1), is significantly slower (2.93 +/- 0.07 x 10(-6) cm(2) s(-1)) than that of beta-cyclodextrin. The results indicate that caution should be exercised when studying host-guest complexation by the so-called 'single point' technique. A novel data treatment is introduced which takes into account the diffusion behavior of all of the species when determining K(a). Experimentally determined diffusion coefficients of complexes are also a useful probe of the size of host-guest complexes.

Journal Article↗

PubMed2000

Conformationally constrained anesthetic steroids that modulate GABA(A) receptors.

Various cyclic ether and other 3 alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar in vitro and in vivo activities to the endogenous 3 alpha-hydroxypregnan-20-ones all had an ether oxygen on the beta-face of the steroid D-ring. These results suggest that for optimal GABA(A) receptor modulation, the hydrogen bond-accepting substituent should be near perpendicular to the plane of the D-ring on the beta-face of the steroid.

Androstanols↗

PubMed1999

Bone mineral density testing and osteoporosis education improve lifestyle behaviors in premenopausal women: a prospective study.

One way to decrease the risk of osteoporosis is to maximize peak bone mass. Peak bone mass may be moderately influenced by lifestyle behaviors: increasing calcium and exercise, decreasing alcohol intake and smoking may increase peak bone mass. We examined the effects of osteoporosis education and bone mineral density (BMD) testing on self-reported lifestyle behaviors in 669 premenopausal women enrolled in a prospective study to assess determinants of peak bone mass. Study participants completed a questionnaire that assessed lifestyle behaviors, received pamphlets about osteoporosis, and had BMD testing. One year later, the women completed a similar questionnaire. After education about osteoporosis and BMD testing, women reported that they were less likely to smoke (odds ratio [OR] = 0.55; 95% confidence interval [95% CI]: 0.28-1.0), consume alcohol (OR = 0.13; 95% CI: 0.04-0.34), and caffeinated beverages (OR = 0. 43; 95% CI: 0.27-0.68). Women were more likely to use calcium supplements (OR = 4.3; 95% CI: 3.04-6.2), vitamin D supplements (OR = 12.6; 95% CI: 7.4-22.9), and drink at least one glass of milk a day (OR = 13.3; 95% CI: 7.8-23.9). Further, women with low bone mass were more likely to use calcium supplements (OR = 1.7; 95% CI: 1.2-2.3) and vitamin D supplements (OR = 1.6; 95% CI:1.1-2.2) compared with women who had normal bone mass. Thus, our intervention improved self-reported lifestyle behaviors in premenopausal women. Such behaviors may ultimately increase peak bone mass and decrease the risk of developing osteoporosis.

Adult↗

PubMed1997

Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Abortion, Habitual↗

PubMed1991

Interaction of CrATP with the phosphorylation site of the sarcoplasmic reticulum ATPase.

The chromium moiety of gamma,beta-bidentate CrATP slowly accepts a ligand from the sarcoplasmic reticulum Ca-ATPase to form an exchange inert coordination complex (k + 1 = 0.083 min-1; k - 2 = 0.003 min-1, 37 degrees C, 100 microM CaCl2). The stability of the Cr3+ coordinate bonds allowed the complex to be isolated by filtration techniques at neutral pH without acid precipitation. We found 4-5 nmol of [gamma-32P]CrATP to bind to 1 mg of sarcoplasmic reticulum protein with the subsequent occlusion of 7-8 nmol of 45Ca2+. At 37 degrees C, the CrATP.ATPase complex could be formed in the absence of Ca2+, although the reaction was 2-3 times slower than in the presence of Ca2+. Inhibition by Pi, by orthovanadate, and by fluorescein 5'-isothiocyanate verified that the bound CrATP was at the catalytic site. The site of CrATP attachment was found to be on the A tryptic fragment, possibly on the A2 subfragment. It was determined that Ca2+ binding to high affinity sites on the enzyme controls the rate by which the Cr3+ moiety accepts the ligand from the enzyme. The rate of change in the EPR spectrum of iodoacetamide spin-labeled ATPase was shown to follow the rate of ligand acceptance, rather than the binding of Ca2+ and substrate per se. This particular change has been attributed to the formation of an activated complex that is immediately precursory to phosphorylation and indicates here that this complex cannot be properly formed until the metal has been chelated by the enzyme. It is concluded that control over metal chelation (Cr3+ here, Mg2+ in the normal mechanism) is one means by which Ca2+ activates the enzyme.

Adenosine Triphosphatases↗

PubMed1985

Fatal and nonfatal accidents on the railways--a study of injuries to individuals, with particular reference to children and to nonfatal trauma.

This paper reports a five-year total population study of fatal railroad accidents involving individuals (that is, not including train crashes or derailments); and a consecutive unselected series of nonfatal isolated injuries in Queensland, Australia. There were 84 fatalities and 211 cases of significant nonfatal traumata. Fatal railway accidents involving children under 15 years of age are now more common in Australia than childhood poisonings and electrocutions. Two syndromes occur--(a) toddlers living near the tracks who simply wander onto the line; and (b) young teenage boys who are run down on level crossings, either as pedestrians or cyclists. Adult fatalities include (a) occupational deaths among railway workers (20%), (b) car-train collisions at level crossings (19%), (c) drunk pedestrians who walk into trains (17%), suicides (12%), and old folk who walk into trains (12%). Of 211 nonfatal cases studied, falls in and from both moving and stationary trains were the most common type of accident. Sudden jolting of the train (probably unpreventable) contributed to 26% of all falls. Twenty-two percent of nonfatal accidents resulted from a person being struck by a train. All persons who survived being struck by a train received serious injuries and required hospital admission. Fatalities involving adults include a high proportion of suicides. Some accidents, such as fingers being caught in windows and doors, can and are being overcome through improved design.

Accidents↗

PubMed1982

Thirty-month demonstration project for treatment of self-injurious behavior in severely retarded individuals.

Eighteen severely and profoundly retarded adolescents were treated in a research and demonstration project within a state institution by behavior modification methods for 30 months. Most showed traits of autism, phobias and persistant vulnerability. Restraints had acquired stimulus control. Programming, an aversive event, evoked SIB as avoidance reaction. Effect of pharmacotropic medication was transitory at best. Combination of several behavior modification techniques obtained complete suppression of SIB in 66.6%, partial in 16.7% and none in 16.7%. Non-aversive behavior modification methods, though slow-acting and time-consuming, produced permanent results in 72.7%. Aversive stimulation by remote controlled ESS suppressed SIB instantaneously and made SIB residents accessible to behavior modification and training. In 43%, durability of extinction was limited, despite concomitant intensive full-day behavior modification programs. Extinction was maintained through booster ESS. In two of seven cases ESS lost its aversive qualities. The use of ESS appears justified when non-aversive treatment modalities have failed and life-threatening situations persist.

Adolescent↗